Overview of the FABULOUS EU Project: Final System Performance Assessment With Discrete Components

In this paper, we present the most comprehensive system demonstrator realized so far inside the FABULOUSproject, an EU 7th Framework Program European research project. The architecture proposed in FABULOUS is based on frequency division multiplexed PON and uses a self-coherent and reflective approach in the upstream. The demonstration presented in this paper uses discrete optoelectronics components. We will show system experiments realized with five active optical network units, together with the emulation of other 27 ONUs ASE noise, demonstrating that such network is capable of an upstream transmission of 32 Gb/s over 40 km of dark fiber and an attenuation of 31 dB, in compliancy with ODN class N2 of the latest PON standards. In addition, we will demonstrate, thanks to the flexibility of frequency multiplexing, that the network can adapt its performances to the link conditions, achieving higher aggregate bit rates or higher losses depending on the link quality that every user in the network experiences. To conclude, we will investigate on the feasibility of the required digital signal processing onto FPGA or ASIC platforms

Refining myositis associated with primary Sjögren’s syndrome: data from the prospective cohort ASSESS

International audienceTo refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS)

Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP

Objectives: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA). Methods: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group “Autoimmunity Testing”; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP). Results: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations. Conclusions: These recommendations are an important step to achieve high quality ANA testing

NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation

The Nck-associated protein 1-like (NCKAP1L) gene, alternatively called hematopoietic protein 1 (HEM-1), encodes a hematopoietic lineage-specific regulator of the actin cytoskeleton. Nckap1l-deficient mice have anomalies in lymphocyte development, phagocytosis, and neutrophil migration. Here we report, for the first time, NCKAP1L deficiency cases in humans. In two unrelated patients of Middle Eastern origin, recessive mutations in NCKAP1L abolishing protein expression led to immunodeficiency, lymphoproliferation, and hyperinflammation with features of hemophagocytic lymphohistiocytosis. Immunophenotyping showed an inverted CD4/CD8 ratio with a major shift of both CD4+ and CD8+ cells toward memory compartments, in line with combined RNA-seq/proteomics analyses revealing a T cell exhaustion signature. Consistent with the core function of NCKAP1L in the reorganization of the actin cytoskeleton, patients' T cells displayed impaired early activation, immune synapse morphology, and leading edge formation. Moreover, knockdown of nckap1l in zebrafish led to defects in neutrophil migration. Hence, NCKAP1L mutations lead to broad immune dysregulation in humans, which could be classified within actinopathies